Table 2.
Summary of demographic and clinical characteristics of patients presenting as COVID-19-associated aHUS.
| Reference | Sex | Age | Known Comorbidities | Reported Signs/Symptoms Associated with COVID-19 | Proposed Underlying Pathophysiology of TMA (Excluding COVID-19) | Biopsy-Proven TMA | PCR/Serology for SARS-CoV-2 | Kidney Function/Serum Creatinine (μmol/L) | Lowest Platelet Count (×106/L) | Accelerated Hypertension | APL Antibodies | TMA-Specific Treatment | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ville [45] | F | 28 | Hereditary aHUS, CKD 3, arterial hypertension | No respiratory symptoms, fever, dysphagia, headache | Heterozygous pathogenic variant in the membrane cofactor protein-encoding gene | Not performed | + PCR, serology not performed | 230 at admission, peaked at 256, 194 at discharge, 176 on follow-up after 1 month | 106 | No | Not assessed | Eculizumab | Partial recovery of renal function |
| El Sissy [46] | M | 66 | Not mentioned | Mild respiratory symptoms | Pathogenic variant of CFH gene, reduced factor H plasma level, mildly increased sC5b-9 | Yes: glomerular + arteriolar thrombi, EC detachment | + PCR, serology not performed | 884 at admission—HD | 50 | Yes | Not assessed | None | Renal failure |
| El Sissy [46] | M | 71 | ESRD due to nephroangiosclerosis, kidney transplant recipient | Moderate respiratory symptoms (low grade oxygen therapy) | Pathogenic variant of C3 gene, very high trough levels of CNI (transplanted kidney) | Yes: performed 3 weeks after TMA resolution; GBM duplication, glomerulosclerosis | + PCR, serology not performed | 203 at admission, 150 (baseline value) after 1 month | 16 | No | Not assessed | TPE, eculizumab | Recovery of renal function to baseline |
| El Sissy [46] | M | 35 | Not mentioned | Mild respiratory symptoms | Pathogenic variant of CFI gene, reduced factor I plasma level, + factor H autoantibodies | Yes: glomerular + arteriolar thrombi | + PCR, serology not performed | 699 at admission—HD | 11 | Yes | Not assessed | TPE, eculizumab | Renal failure |
| El Sissy [46] | F | 26 | ESRD due to focal segmental glomerulosclerosis, kidney transplant recipient | Mild respiratory symptoms | Risk haplotype in the membrane-cofactor protein gene, + factor H autoantibodies, CNI (transplanted kidney) | Not performed | + PCR, serology not performed | 637 at admission, 371 after 4 months | 22 | Yes | Not assessed | TPE, eculizumab, rituximab | Partial recovery of renal function |
| Mat [47] | M | 39 | IgA nephropathy, CKD 3, hypertension, esophagitis | No respiratory symptoms, diarrhea, fever | C3 gene mutation | Yes: GBM duplication, mucoid thickening + obliteration of the lumen of a small artery | Both + | 416 at admission, became HD-dependent during hospitalization | 80 | No | Negative | TPE, steroids, eculizumab | Renal failure |
| Kurian [48] | F | 31 | No comorbidities | No respiratory symptoms, headache, nausea, diarrhea | Low C4, + factor H autoantibodies | Not performed | + PCR, serology not performed | 540 at admission, HD-dependent during hospitalization, 97 on follow-up | 25 | No | Not assessed | TPE, steroids, eculizumab | Partial recovery of renal function |
| Kurian [48] | M | 25 | Previous episode of TMA following influenza A | No respiratory symptoms, nausea, malaise, fever | Decreased C3, normal C4 | Not performed | + PCR, serology not performed | 219 at admission, peaked at 653 (no HD), 89 2 weeks after discharge | 32 | No | Not assessed | TPE, eculizumab | Complete recovery of renal function |
| Korotchaeva [49] | F | 49 | Not mentioned | No respiratory symptoms, abdominal pain, diarrhea, vomiting, fever | Decreased C3, increased C5b-9 | Yes: mucoid swelling of arterioles, glomerular capillary loops ischemia | + PCR, serology not performed | 210 at admission, peaked at 558—HD, 300 after 4 months | 157 | No | Negative | Eculizumab | Partial recovery of renal function |
| Pinte [50] | M | 23 | Arterial hypertension, previous episodes of accelerated hypertension | No respiratory symptoms, headache | Heterozygous variant with unknown significance in CFI, risk polymorphisms in CFH | Yes: glomerular capillary lumina occluded by fibrin thrombi, severely narrowed or occluded arterial lumina | + PCR, serology not performed | 424 at admission, peaked at 946—HD | 125 | Yes | + lupus anticoagulant | None (late diagnosis, lack of availability of eculizumab) | Renal failure |
| Utebay [51] | M | 76 | Atrial fibrillation | Dyspnea, cough, cardiogenic shock | Severely decreased complement levels | Not performed | + PCR, serology not performed | 88 at admission, peaked at 357—RRT, 170 at discharge | 12 | No | Negative | TPE, steroids, eculizumab | Partial recovery of renal function |
| Logan [52] | M | 40 | No comorbidities | Weakness, fever, altered mental status | Dysregulation of the alternative pathway of the complement | Not performed | + (test not specified) | 714 at admission—HD, improvement during hospitalization (not further specified) | 7 | No | Not assessed | TPE | Recovery of renal function |
| Jhaveri [53] | F | 69 | Asthma | Cough, fever, dyspnea | Low factor H, HCQ | Yes: widespread glomerular thrombi | Both + | 64 at admission, required HD later on | 14 | No | Elevated β-2-GPI IgM, other negative | Eculizumab | Died |
| El Sissy [46] | F | 38 | ESRD due to IgA nephropathy, kidney transplant recipient | Mild respiratory symptoms | CNI (transplanted kidney) | Yes: extensive EC detachment from GBM | + PCR, serology not performed | 283 at admission, 159 (baseline value) 6 months after treatment | 103 | No | Not assessed | None (decrease in tacrolimus dosage) | Recovery of renal function to baseline |
| Bascunana [54] | M | 40 | ESRD due to Liddle syndrome, kidney transplant recipient | Fever, dyspnea, diarrhea, abdominal pain | HCQ, CNI (transplanted kidney) | Not performed | + PCR, serology not performed | 326 at admission, peaked at 777—HD, 168 at discharge | 12 | No | Negative | TPE | Recovery of kidney function |
| Jespersen Nizamic [55] | F | 49 | ESRD due to FSGS, kidney transplant recipient | No respiratory symptoms, diarrhea, menorrhagia, acute pancreatitis | CNI (transplanted kidney) | Yes: significant narrowing/obliteration of the hilar arteriolar lumina, intimal edema, fragmented RBC and fibrin thrombi | + PCR, serology not performed | 357 at admission, peaked at 539, 151 10 days after discharge | 52 | No | Not assessed | Reduced dose of CNI | Complete recovery of kidney function |
| Sharma [56] | F | 63 | Metastatic cholangiocarcinoma | Dyspnea | Metastatic carcinoma, gemcitabine | Yes: Acute features of TMA–not further specified | Not specified | Approximately 100 at admission, peaked at approximately 640—HD | 53 | No | Not assessed | TPE, steroids | Palliative care, no data on kidney function |
| Tarasewicz [57] | M | 41 | ESRD due to IgA nephropathy, kidney transplant recipient | Diarrhea, hypertension; presented with pneumonia 1 month earlier | CNI (transplanted kidney) | Yes: fragmented RBCs within edematous glomerular capillary walls | + PCR 1 month prior | 325 at admission, started HD 4 months later | 115 | Yes | Not assessed | TPE | Graft failure |
| Safak [58] | M | 34 | Arterial hypertension | Blurred vision | Severe hypertension (after normalization of hypertension, TMA did not resolve) | Not performed | + PCR, serology not performed | 433 at admission, 106 at follow-up | 28 | Yes | Negative | Eculizumab | Complete recovery of renal function |
| Gill [59] | M | 32 | Childhood leukemia, orthotopic heart transplant, CKD 3 | Fever, cough, dyspnea, chest pain | Sirolimus (transplanted heart) | Yes: fibrin thrombi in arterioles without endocapillary hypercellularity or inflammation | Not specified | 685 at admission, 424 7 days after eculizumab, 202 at discharge | 43 | No | Negative | TPE, eculizumab, ravulizumab | Complete recovery of renal function |
| Aminimoghaddam [60] | F | 21 | Drug addict (amphetamine) | Fever, dry cough | Pregnancy, HCQ | Not performed | + PCR, serology not performed | 495 at admission, 80 at discharge | 20 | No | Negative | TPE | Complete recovery of renal function, stillbirth |
| Boudhabhay [61] | M | 46 | Arterial hypertension, obesity | No COVID-19 associated symptoms | Elevated C5b9, low C4, genetic testing insignificant | Yes: glomerular fibrin thrombi, myxoid intimal alterations of arterioles and arteries | − PCR, + IgG | 169 at admission, peaked at 660-RRT, 109 at discharge | 90 | Yes | Negative | Eculizumab | Complete recovery of renal function |
| Dorooshi [62] | F | 81 | Arterial hypertension | Fever, dry cough, dyspnea, anorexia, vomiting | Not known | Not performed | + PCR, serology not performed | 805 at admission | 52 | No | Not assessed | None | Died before treatment |
| Airoldi [63] | M | 56 | Liver cirrhosis (Child–Pugh B), HCV | Bilateral pneumonia | HCV, fondaparinux | Not performed | + PCR; serology not performed | No data | 36 | No | Not assessed | Steroids | Recovered, no data on kidney function |
| Korotchaeva [49] | M | 39 | Not mentioned | Fever, dry cough, malaise, dyspnea, anosmia | Not known | Not performed | + PCR, serology not performed | 1035 at admission—HD | 51 | Yes | Negative | TPE, steroids, eculizumab | Renal failure |
| Korotchaeva [49] | F | 66 | Diabetes mellitus type 2 | ARDS | Not known | Not performed | + PCR, serology not performed | 70 at admission, peaked at 193 | 6 | No | Negative | FFP transfusions, tocilizumab, eculizumab | Died |
| Elkayam [64] | F | 44 | No comorbidities | Fever, dry cough, dyspnea | Not known | Not performed | + PCR, serology not performed | 194 on day 2, worsened to HD dependency (not further specified) | 18 | No | Not assessed | TPE, FFP | Partial recovery of renal function |
| Gandhi [65] | M | 27 | Arterial hypertension, CKD | Cough, lethargy, effort intolerance, loss of vision, jejunal perforation | Not known | Yes: ischemic glomerular injury, fibrin deposition and fragmented RBCs in interlobar arterial wall | + PCR, serology not performed | 1963 at admission—HD | Lack of data | Yes | Not assessed | High-dose methylprednisolone, bevacizumab, eculizumab | Renal failure |
Legend: aHUS, atypical hemolytic uremic syndrome; APL, antiphospholipid; CKD, chronic kidney disease; CFH, complement factor H; CFI, complement factor I; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; EC, endothelial cells; ESRD, end-stage renal disease; FFP, fresh frozen plasma; GBM, glomerular basement membrane; GPI, glycoprotein; HCV, hepatitis C; HCQ, hydroxychloroquine; HD, hemodialysis; PCR, polymerase chain reaction; RRT, renal replacement therapy; TMA, thrombotic microangiopathy; TPE, therapeutic plasma exchange.